PHASE-II STUDY OF GEMCITABINE IN PATIENTS WITH ADVANCED PANCREATIC-CANCER

The efficacy and safety of gemcitabine at a starling dose of 800 mg m( 2) administered once a week for 3 weeks with 1 week's rest was investi gated in chemonaive patients with advanced and/or metastatic pancreati c cancer. Of 34 patients, 32 were evaluable for efficacy, 20 patients had metastatic stage IV disease, 25 had a performance status of 1 and 26 (76%) patients has significant pain on presentation. All responses were independently validated by an external oncology review board: two patients achieved a partial response that lasted 5.8 and 5.2 months ( 6.3%) and six patients were stable for at least 4 weeks. The median du ration of survival for evaluable patients was 6.3 months (range 1.6-19 .2 months). The tumour markers, CEA, CA 19-9 and CA 195 were serially measured in 16 patients. There was a good correlation with tumour resp onse when all three markers were significantly decreased. In 4 of 16 p atients, tumour marker levels decreased by greater than or equal to 60 %, including the two responders, one patient who survived for 12 month s and one patient who showed objective tumour shrinkage but was deemed ineligible for response evaluation because the disease was considered not to be bidimensionally measurable. Symptomatic benefits included i mprovement in performance status (17.2%), analgesic requirement (7.4%) , pain score (28.6%) and nausea (27.3%). The mean number of cycles adm inistered was 2.5 and the mean dosage received was 890 mg m(2) per inj ection. Seventy-four per cent of dose administrations were given on sc hedule. Toxicity, particularly haematological toxicity, reported as th e maximum WHO grade experienced by patients was mild. Infective episod es were rare and limited to WHO grade 2, (6.7%). Nausea and vomitimg w as generally modest (WHO grade 3, 26.7%). Other side-effects included mild transient flu-like symptoms (seven patients) and peripheral oedem a (three patients), which was not associated with abnormal cardiac hep atic or renal function. Gemcitabine has modest activity in pancreatic cancer, a limited positive improvement on a range of patient benefit p arameters and has a mild toxicity profile. For these reasons and becau se of its novel mode of action, gemcitabine warrants further investiga tion in combination studies in pancreatic cancer.